Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK.

Abstract

Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; especially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4 °C in IGL-1 or HTK preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.

• Authors: Arnau Panisello-Roselló, Eva Verde, Alexandre Lopez, Marta Flores, Emma Folch-Puy, Anabela Rolo, Carlos Palmeira, Georgina Hotter, Teresa Carbonell, René Adam, Joan Roselló-Catafau
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 19 Issue 2 (Jan 24 2018) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 29364854 (Publication Type: Journal Article)

Chemical References

• Biomarkers
• Bretschneider cardioplegic solution
• HMGB1 Protein
• IGL-1 solution
• Organ Preservation Solutions
• Mannitol
• Procaine
• Potassium Chloride
• TOR Serine-Threonine Kinases
• Glucose

Topics

• Animals
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Biomarkers
• Cold Ischemia (adverse effects, methods)
• Cryopreservation
• Cytoprotection
• Fatty Liver (metabolism, pathology)
• Gene Expression
• Glucose
• HMGB1 Protein (genetics, metabolism)
• Histocytochemistry
• Liver Function Tests
• Liver Transplantation (methods)
• Male
• Mannitol
• Microscopy, Confocal
• Mitochondria, Liver (drug effects, metabolism)
• Organ Preservation (methods)
• Organ Preservation Solutions
• Phosphorylation
• Potassium Chloride
• Procaine
• Rats
• Reperfusion Injury (metabolism, prevention & control)
• TOR Serine-Threonine Kinases (metabolism)